The present project is the continuation of a study which aims at further understanding the pathogenesis of congenital cytomegalovirus (CMV) infection in humans using the guinea pig as an animal model. Experiments are designed to define the consequences of maternal primary guinea pig CMV infection, reinfection and reactivation on congenital infection. In addition, the contribution of humoral and cell mediated immunity to the control of maternal and congenital guinea pig CMV infection are also investigated. Further studies of primary guinea pig CMV infection during gestation will define the range of histopathology in the offspring. The proposal also includes experiments which will assess virus distribution and histopathology during maternal guinea pig CMV reinfection and reactivation. The possible effects on fetuses and newborns will also be evaluated. Host immune responses to CMV will be explored during maternal and congenital infection. The project proposes to use a specific delayed skin test for measuring the in vivo immune response of guinea pigs during CMV infection. Experiments for testing in vitro the cell mediated immunity to CMV infection are also included. The data collected from these studies of the guinea pig model should help define the host defense mechanisms involved in maternal and congenital CMV infection. The information obtained will be useful in explaining the problems associated with human congenital CMV infection.